HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 45, 42575-42579, November 9, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/45/42575    most recent M107724200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oh, S.-M. Articles by Choi, S.-Y. Search for Related Content PubMed PubMed Citation Articles by Oh, S.-M. Articles by Choi, S.-Y. Social Bookmarking                      What's this?

Human Neutrophil Lactoferrin trans-Activates the Matrix Metalloproteinase 1 Gene through Stress-activated MAPK Signaling Modules^*

Sang-Muk Oh, Dae Hyun Hahm, Ik-Hwan Kim, and Sang-Yun Choi^§

From the Division of Life Sciences, Graduate School of Biotechnology, Korea University, Seoul 136-701, Korea

It has been proposed that human neutrophil lactoferrin (Lf) could be involved in gene expression as a DNA-binding protein after its translocation into the nucleus. However, the molecular basis of Lf action has not been defined, and Lf-regulated target genes have not been identified. We report here that overexpressed Lf functions as a specific trans-activator of matrix metalloproteinase 1 (MMP1) gene, and that induction of this AP-1-responsive gene is mediated via the stress-activated MAPK signaling modules. Transactivation of the MMP1 promoter by overexpressed Lf requires the presence of an AP-1 binding site. In gel shift experiments, Lf did not interact directly with AP-1-containing fragments of the MMP1 promoter. However, nuclear extracts from Lf-expressing cells contained increased levels of proteins that bound to AP-1 elements. This Lf-induced AP-1 DNA binding activity was reduced by a p38 MAPK inhibitor. Inhibitors of the MEK kinases had little effect on Lf-induced AP-1. However, expression of dominant-negative MKK4 or JNK1 inhibited Lf-induced gene expression. The JNK activity stimulated by Lf correlates with the enhanced AP-1 binding ability. These findings demonstrate that the Lf-induced activation of AP-1 is mediated via JNK and p38 MAPK pathways.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S.-M. Oh, S.-H. Lee, B.-J. Lee, C.-W. Pyo, N.-K. Yoo, S. Y. Lee, J. Kim, and S.-Y. Choi A Distinct Role of Neutrophil Lactoferrin in RelA/p65 Phosphorylation on Ser536 by Recruiting TNF Receptor-Associated Factors to I{kappa}B Kinase Signaling Complex J. Immunol., November 1, 2007; 179(9): 5686 - 5692. [Abstract] [Full Text] [PDF]

				H. Wakabayashi, N. Takakura, K. Yamauchi, and Y. Tamura Modulation of Immunity-Related Gene Expression in Small Intestines of Mice by Oral Administration of Lactoferrin Clin. Vaccine Immunol., February 1, 2006; 13(2): 239 - 245. [Abstract] [Full Text] [PDF]

				C. C. Taggart, S.-A. Cryan, S. Weldon, A. Gibbons, C. M. Greene, E. Kelly, T. B. Low, S. J. O'Neill, and N. G. McElvaney Secretory leucoprotease inhibitor binds to NF-{kappa}B binding sites in monocytes and inhibits p65 binding J. Exp. Med., December 19, 2005; 202(12): 1659 - 1668. [Abstract] [Full Text] [PDF]

				Y. Takayama, H. Takahashi, K. Mizumachi, and T. Takezawa Low Density Lipoprotein Receptor-related Protein (LRP) Is Required for Lactoferrin-enhanced Collagen Gel Contractile Activity of Human Fibroblasts J. Biol. Chem., June 6, 2003; 278(24): 22112 - 22118. [Abstract] [Full Text] [PDF]